Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients with Locally Advanced Bladder Cancer - Expert Commentary

Methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) neoadjuvant chemotherapy is a standard of care for muscle-invasive urothelial bladder cancer. However, gemcitabine-cisplatin (GC) is equally effective and associated with less toxicity in the metastatic setting. This has been extrapolated to the neoadjuvant setting in clinical practice. A recent study by Niedersüss-Beke et al. in the journal Oncology prospectively evaluated the clinical outcomes of neoadjuvant GC in patients with locally advanced urothelial cancer.

The investigators prospectively evaluated 87 patients in two centers who received three cycles of neoadjuvant GC prior to radical cystectomy. The clinical endpoint of the study was pathologic response. The secondary endpoints were safety, progression-free survival (PFS), and overall survival (OS). Overall GC was well tolerated, with 83/87 patients completing chemotherapy of whom 80 were evaluable for the primary endpoint. One of the important findings of this study was that 22.5 % of patients achieved pathologic complete response (pCR) was achieved in 22.5% and near pCR was seen in 33.7% of the patients. This resulted in an overall response rate of 45%. In the SWOG trial, MVAC led to a pCR rate of 38%, however it is worth noting that the population in the SWOG trial had a lower median age. As expected, all the patients achieving pCR or near pCR with GC had a higher PFS. Grade 3/4 toxicities occurred in 38% of the patients receiving GC. None of the patients developed febrile neutropenia.

It is important to recognize that a prospective randomized head-to-head comparison between MVAC and GC in the neoadjuvant setting would be the “gold standard” for evaluating the differences in efficacy and toxicity between the two regimens. While this prospective study was not a randomized comparison, it supports the use of neoadjuvant GC as a treatment option for patients with locally advanced bladder cancer.

Written by: Bishoy Faltas MD

References:
Niedersüss-Beke D, Puntus T, Kunit T, Grünberger B, Lamche M, Loidl W, Böhm R, Kraischits N, Kudlacek S, Schramek P, Meran JG. Neoadjuvant Chemotherapy with Gemcitabine plus Cisplatin in Patients with Locally Advanced Bladder Cancer. Oncology. 2017 Apr 12. doi: 10.1159/000463389.
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